The present invention relates generally to drug prescription practices for healthcare providers. More particularly, this invention relates to a system and method for diagnostic monitoring of drug and biomarker levels, relating these measured levels to other patient-specific characteristics, and utilizing this real-time and measurement-based drug level data for optimizing medication choice and dosages for patients taking more than one medication.
Therapeutic Drug Monitoring (TDM) is a term that describes the measurement of drug exposure in, e.g., serum or plasma to tailor dosing in an individual patient. Tailored dosing in individuals is necessary because a multitude of parameters, such as body weight, overall health, patient behavior, and genotype underlie variable drug exposure in patients administered the same dose of a given medication. Different exposures result in different outcomes. For some drugs, such as the blood thinner Warfarin™, TDM is routine, with the physician starting, on a patient by patient basis, with very low doses and slowly titrating to efficacious blood levels to avoid potentially fatal bleeding.
TDM is not routinely practiced with most medications, not because exposure is any less dependent on individual patient parameters, but because it is not deemed necessary when the margin between efficacy and toxicity is wide. Therefore, TDM is typically deployed to avoid toxicity rather than to maximize the effectiveness of individual drugs.
Drug exposure is not only dependent upon the physical makeup of individual patients, but also upon interactions with other drugs that are concomitantly administered. Drug-drug interactions (DDI's) have a substantial impact upon patient outcomes, even with very commonly administered medications. Simvastatin™, for example, is one of the world's most prescribed medications. Co-administration of drugs that inhibit metabolic enzymes and transporters, such as cyclosporine, can drive Simvastatin™ exposure in individual patients upward more than ten-fold, increasing incidence of rhabdomyolysis, a serious and sometimes fatal toxicity of the muscle. This type of interaction is common, and nearly all new medications brought to market carry with them some interaction potential as either a perpetrator or victim of drug-drug interactions despite the best efforts of the pharmaceutical industry (“pharma”).
One key point which is worth considering is that nominal therapeutic ranges of Simvastatin™ and virtually all other drugs are known or at least predetermined. Exposure and identification of medications outside of their range may be easily monitored by measuring drug levels in blood, but measuring drug exposure, especially the exposure of multiple drugs in unison, is not standard practice today. Assays that combine the measurement of drugs and biomarkers in multiplex format to decrease diagnostic costs while streamlining prescribing practices are further not previously implemented in the art.
The influence of genetics, patient characteristics and behaviors, environment, and drug-drug interactions on patient outcomes have all been studied on an individual basis, but currently have little impact on physician prescribing habits. Currently, a physician cannot account for the inherent complexity these parameters impart when prescribing a new medication to a patient, especially given that patients over 65 years of age are often taking 8 or more medications simultaneously. In fact, prospectively building models that predict drug exposure in an individual patient's overall treatment regimen to help guide physicians in drug selecting and dosing would require a comprehensive data set that simply does not exist today. Drug exposure in the light of complexity must be quantified if we are to understand drivers of patient variability.
Therefore, what is needed is a system and/or method for measuring the exposure of all concomitant medications in individual patients and a means to apply this information to inform physician prescribing practices. Such systems and methods may desirably serve one or more purposes including but not limited to: providing a real-world diagnostic monitoring; enabling better prescribing practices resulting in reduced risk for patients; yielding more effective treatment outcomes by increasing compliance, decreasing hospitalizations and optimizing medication choice; streamlining costs by integrating biomarker and therapeutic drug monitoring assays; producing valuable data necessary for prospective modeling of patient characteristics and reporting measures for better drug development in the future; and yielding critical insights on the benefit-risk and the real world effectiveness of pharmaceutical products for regulators, payers, HTA agencies, pharma and ultimately, patients.
It would be desirable that such systems and methods produce results easily for presentation to the physician in a simple format such that prescribing practices can be optimized for each patient in, e.g., a fifteen minute consultation.
Therefore, it would further be desirable to restrict the amount and scope of information provided, and to present this information in a graphical format with clear recommendations.
It is still further desirable that empirical tools implemented by a system and method as disclosed herein demonstrate where medical records for patients are wrong (e.g., they do not inform multiple physicians of medications that the patient is actually taking), compliance is poor (e.g., where patients are not taking medications prescribed to them), and medication duplicity is common (e.g., multiple medications of the same class are co-prescribed).